P975: INTERIM ANALYSIS OF PHASE II STUDY OF DARATUMUMAB IN COMBINATION WITH BORTEZOMIB AND DEXAMETHASONE IN PATIENTS WITH MULTIPLE MYELOMA WHO RECEIVED 1 PRIOR LINE OF THERAPY (KMM1906)
Authors: K. H. Yoo, G. W. Gang, J. H. Yi, M. K. Kim, H. J. Kim, S.-H. Kim, J. S. Park, J.-J. Lee, C.-K. Min, J. H. Lee, D. Cho, K. Kim
Journal: HemaSphere (2022)

Background: Daratumumab in combination with bortezomib and dexamethasone (DVd) demonstrated efficacy in heavily pretreated patients with relapsed or refractory multiple myeloma (MM). In a previous pivotal phase 3 study, DVd showed better efficacy in patients receiving only first-line treatment, while the limited administration of bortezomib and dexamethasone for 8 cycles was criticized. Aims: We conducted a phase 2 study with DVd regimen in patients with MM who received 1 prior line of therapy. Methods: We evaluated daratumumab (16 mg/kg IV), bortezomib (1.3 mg/m2 SQ), and dexamethasone (20 mg IV or PO) with maintaining all three drugs after 9 cycles until disease progression or unacceptable toxicity. The primary endpoint was objective response rate ≥ very good partial response (VGPR). Secondary objectives included progression-free survival (PFS), overall survival (OS), safety and tolerability, and minimal residual disease (MRD)-negativity. MRD was assessed in patients who achieved in stringent complete response (sCR) or CR, and who maintained VGPR over 6 months, with EuroFlow-based next-generation flow (NGF). Results: From June 2020 to June 2021, 26 MM patients who received 1 prior line of therapy and disease progressed were enrolled at 10 centers in Korea. The median age of all patients was 72 years (range, 47-85), and 8 patients were male. Five patients (19%) had high-risk cytogenetic abnormalities (t(4;14), t(14;16), or del17p), and 6 patients (23%) had extramedullary disease. All patients were treated with 1 prior line, including VTD (N = 11, 42%), VMP (N = 8, 31%), Rd (N = 6, 23%), and CMP (N = 1, 4%). Nineteen patients (73%) and 18 patients (69%) were exposed to bortezomib and immunomodulatory drugs, respectively, from previous treatment (Table 1). During the median follow-up period of 11.7 months, 15 patients (58%) maintained treatment, and 11 patients (42%) discontinued the study due to disease progression (N = 6), death from other causes (N = 2), or withdrawal of consent (N =3). 16 patients (62%) achieved ≥ VGPR (2 sCR, 7 CR, and 7 VGPR). The MRD-negativity (10-5) was 5/12 (42%) (Table 2). The treatment response and PFS of each patient were given in the swimmer plot (Figure 1). The most common adverse event (AEs) ≥ grade 3 was thrombocytopenia (N = 6, 23%). Serious AEs were reported in 8 patients (31%). Dose delay or dose reduction have occurred in 17 patients (65%). Table 2. - Response and MRD-negativity rates Response category No. with response (%) CR or better 9 (35%) sCR 2 (8%) CR 7 (27%) VGPR or better 16 (62%) VGPR 7 (27%) PR 6 (23%) MR 2 (8%) SD 2 (8%) PD 0 MRD-negativity (10-5) N = 12 Negative 5 (42%) Image:Summary/Conclusion: Among patients with MM who received 1 prior line of therapy, DVd regimen with maintenance strategy showed an acceptable clinical response and MRD-negativity with manageable toxicity profile.